3-[4-(5-nitro-2-furyl)-2-thiazolylamino]-2-oxazolidinone



United States Patent Office 3,149,119 Faterited Sept. 15, 1964 This invention relates to new chemical compounds and to processses for the preparation thereof. More particularly this invention is concerned with a new chemical compound 3-[4-(5-nitro-2-furyl) 2 thiazolylamino1-2- oxazolidinone having chemotherapeutic activity and represented by the formula:

--NHN-C:\-O II 1 (MN N o Hie-0H1 (I) with a new chemical compound 1-(2-oxo-3-oxazolidinyl)- 2-thiourea useful in synthesis and represented by the formula:

HzC-CHa (II) and With processes for the preparation of these compounds.

The new compound of Formula I is distinguished by its chemotherapeutic activity in the prevention and treatment of a broad spectrum of parasitic infections in poultry and animals when administered in far less than toxic amount. Protozoan disesaes in poultry provoked by organisms such as Histomonas meletzgridis and Eimeria tenella are efiectively combatted by the administration in the feed supply of from about 0.0ll0.022% by Weight of this compound. Bacterial infections are readily susceptible to this new compound; for instance, mice lethally infected by Staphylococcus aurezzs or Salmonella typhosa are protected from death by the oral administration of as little as 105 rug/kg. Trypanosome infections also yield to this compound; for instance, mice infected with Trypanosoma foetus are ridded of this organism by the oral administration of dosages of about 30 mgjkg. over a four-day period. Helminthic infections are similarly susceptible to treatment with this compound; for instance, mice harboring Syphacz'a obvelaza are relieved by the administration b.i.d. of 50 mg./kg. for four days.

This compound is relatively non-toxic. In mice the highest tolerated dose of it is greater than 1000 rug/kg. Its administration at a level of 0.022% in the diet of turkeys and chickens has manifested no sign of toxic efiect.

The broad antimicrobial therapeutic efiectiveness and low toxicity of this compound makes it a valuable medicinal agent.

The new compound represented by Formula II is useful in synthesis. It is valuable as an intermediate in the production of the compound of Formula I. In accordance with this invention it is readily prepared by reacting 3-amino-2-oxazolidone with an alkali thiocyanate such as potassium thioacyanate in an aqueous medium and in the presence of a mineral acid such a hydrochloric. To facilitate its preparation, heat may be supplied to the reaction mixture. The product 1-(2-oxo-3-oxazolidinyl)- 2-thiourea is readily recovered by cooling and filtering the reaction mixture.

The compound represented by Formula I is readily prepared by bringing together a halornethyl 5-nitro-2- furyl ketone and the compound represented by Formula ii. In accordance with this invention, the process currently preferred consists in mixing bromomethyl 5-nitr0-2- furyl ketone and l-(Z-oxo-S-oxazolidinyl)-2-thiourea in an inert medium such as ethanol and heating until reaction is complete. It is advantageous to stir the reaction mixture to bring about good dispersion and contact of the reactants. The reaction mixture is cooled and the product filtered. It may be recrystallized from a suitable solvent such as ethanol, if desired.

The compound represented by Formula I can be compounded in various pharmaceutical forms such as tablets, capsules, suspensions, troches, and the like using excipients and adjuvants common to the art of pharmacy. When used in the veterinary field a convenient form of administration is through admixture in the feed supply.

in order that this invention may be readily available to and understood by those skilled in the art, the following examples are given:

EXAMPLE I 1-(2-0x0-3-Oxaz0lidinyl) -2-Thi0urea A solution of 3-amin0-2-0Xazolid0ne (60 g., 0.6 mole) and potassium thiocyanate g., 0.67 mole) in ml. of water is treated With 50 ml. of concentrated hydrochloric acid and heated on the steam bath for 1 /2 hours. After cooling, the solid (72.5 g.) is filtered. It may be recrystallized from 1380 ml. of Water. The yield of pure material is 62 g. (64%); M.P. 195-196".

EXAMPLE II A mixture of 46.8 g. (0.2 mole) of bromoethyl S-nitro- 2-fury1 ketone and 32.2 g. (0.2 mole) of 1-(2-oxo-3-oxazolidinyl)-2-thiourea in 500 ml. of alcohol is refluxed for 1 hour with stirring. After cooling, the yellow solid (53.2 g., M.P. 165) is filtered and recrystallized from 1600 ml. of alcohol. The yield of 3-[4-(5-nitro-2-furyD-2- thiazolylamino]-2-oxazolidinone is 45.3 g. (77%); MP. -173 What is claimed is:

The compound 3-[4-(5-nitro-2-furyl) 2 thiazolylamino]-2-oxazolidinone represented by the formula:

Ego-CH2 References Cited in the file of this patent UNITED STATES PATENTS 2,647,905 Surrey Aug. 4, 1953 2,709,172 Dodson May 24, 1955 2,755,285 ONeill et a1 July 17, 1956 2,868,801 Steele Jan. 13, 1959 2,891,962 Smith et a1 June 23, 1959 3,004,002 Kaplan et al Oct. 10, 1961 OTHER REFERENCES Degering: Outline of Organic Nitrogen Compds, p. 459 (1945).

Wiley et al.: Organic Reactions, v01. VI, pp. 369- 373, 378 (1951) Elderfield: Heterocyclic Compounds, vol. 5, p. 401 (1957).

UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No. 3,149, 119 September 15 1964 Frank Frederick Ebetino It is hereby certified that error appears in the above numbered patent requiring correction and that the said Letters Patentshould read as corrected below.

Column 2, line 37, for "bromoeth'y l" read bromomethyl- Signed and sealed this 12th day of January 1965.

(SEA-L) Attest:

EDWARD J. BRENNER ERNEST W. SWIDER Commissioner of Patents Aitesting Officer 

